Department of Public Health, Umeå University, Umeå, Sweden.
Ann Rheum Dis. 2012 Jun;71(6):825-9. doi: 10.1136/annrheumdis-2011-200668. Epub 2011 Nov 29.
Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years.
To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk factors.
51 multicase families consisting of 163 individuals with rheumatoid arthritis (RA) (mean±SD age, 60±14 years; disease duration 21 years; 71.8% female) and with 157 first-degree relatives unaffected by RA (54±17 years; 59.9% female) were recruited. Isotypes of antibodies against CCPs (IgG, IgA and IgM) and RFs (IgM and IgA) were determined using automated enzyme immunoassays. Cut-off levels were established using receiver operating characteristic curves based on values for 100 unrelated healthy controls.
The concentrations and frequencies of all anti-CCP and RF isotypes were significantly increased in first-degree relatives and patients with RA compared with unrelated healthy controls. The relative distribution of IgA and IgM isotypes was higher than IgG in the relatives, whereas the IgG isotype dominated in patients with RA. The patients carried human leucocyte antigen-shared epitope (HLA-SE) significantly more often than the relatives (71.4% vs 53.9%, p=0.01), while the frequency of the PTPN22 T variant was similar. HLA-SE, combined with smoking, was significantly related to all combinations of anti-CCP and RF isotypes in patients with RA. No such relationships were found for the first-degree relatives.
All anti-CCP and RF isotypes analysed occurred more commonly in unaffected first-degree relatives from multicase families than in controls, but with different isotype distribution from patients with RA.
类风湿因子 (RF) 和针对 IgG、IgA 和 IgM 免疫球蛋白型环瓜氨酸肽的抗体已被证明可在疾病发病前数年出现。
评估多病例家族一级亲属的血清学风险标志物与遗传和环境风险因素的关系。
共纳入 51 个多病例家族的 163 名类风湿关节炎 (RA) 患者（平均年龄 ± 标准差，60 ± 14 岁；病程 21 年；71.8%为女性）和 157 名未患 RA 的一级亲属（平均年龄 ± 标准差，54 ± 17 岁；59.9%为女性）。采用自动化酶免疫分析法测定抗 CCP（IgG、IgA 和 IgM）和 RF（IgM 和 IgA）抗体的同型。根据 100 名无关健康对照者的数值，使用受试者工作特征曲线确定截断值。
与无关健康对照组相比，一级亲属和 RA 患者的所有抗 CCP 和 RF 同型的浓度和频率均显著升高。与 RA 患者相比，亲属中 IgA 和 IgM 同型的分布比例高于 IgG，而 IgG 同型在 RA 患者中占主导地位。RA 患者携带人类白细胞抗原共享表位 (HLA-SE) 的频率明显高于亲属（71.4%比 53.9%，p=0.01），而 PTPN22 T 变体的频率相似。HLA-SE 与吸烟相结合与 RA 患者的所有抗 CCP 和 RF 同型均显著相关。在一级亲属中未发现这种关系。
在多病例家族中，未受影响的一级亲属中分析的所有抗 CCP 和 RF 同型比对照组更常见，但与 RA 患者的同型分布不同。
